Is DUSP5 p.Pro120Ser (c.358C>T) pathogenic?

DUSP5 p.Pro120Ser (c.358C>T) is classified Uncertain significance in DUSP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: ambiguous (0.363); Very rare (popmax 0.00141%, afr).

How common is DUSP5 p.Pro120Ser (c.358C>T) in the general population?

DUSP5 p.Pro120Ser (c.358C>T) is very rare (popmax 0.00141%, afr) (gnomAD).

What do computational predictors say about DUSP5 p.Pro120Ser (c.358C>T)?

AlphaMissense predicts ambiguous (score 0.363) — an in-silico prediction, not a clinical call.

DUSP5 p.Pro120Ser

c.358C>T · VCV3842941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00141%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.363	ambiguous
REVEL	0.08	moderately benign-leaning
SaProt	LLR -9.10	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -1.8, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 8,933 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00141% African / African-American · 1/70,816 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000194% 3/1,543,648 alleles · very rare exomes 2/1,391,528 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00141%	70,816
European (non-Finnish)	0.000173%	577,231

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DUSP5
Protein: p.Pro120Ser
Coding: c.358C>T
MANE Select: NM_004419
Type: single nucleotide variant
Location: chr10:110498479 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.76 · 1 PDB
Residue 120: the rhodanese domain

Full DUSP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP5 p.Asp291Asn Uncertain significance ★★ ⚠ same type
DUSP5 p.Ala55Ser Benign ★★ same type
DUSP5 p.Ala104Val Uncertain significance ★ ⚠ same type
DUSP5 p.Ala59Pro Uncertain significance ★ ⚠ same type
DUSP5 p.Arg121Leu Uncertain significance ★ ⚠ same type
DUSP5 p.Arg16Ser Uncertain significance ★ ⚠ same type
DUSP5 p.Arg213Gln Uncertain significance ★ ⚠ same type
DUSP5 p.Arg269Cys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dusp5-p-pro120ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown